The goal of this project is to evaluate the contribution of genetic and environmental factors to the etiology of Parkinson's disease. We propose a four year study in the prevalent cases of Parkinson's disease in a unique, population-based twin registry, maintained by the National Academy of Sciences National Research Council. There are approximately 6,000 surviving pairs in which both members are still living in this cohort, formed from white male twins born between 1917-1924 and both serving in the US military. Prevalent cases will be identified by a three-step process, beginning with a brief telephone screen, followed by a more detailed telephone interview and finalized by a neurologic examination. Co-twins of all affected twins will also be examined. Applying community-based incidence estimates, we estimate between 110 - 120 prevalent cases of Parkinson's disease in 1993. The contribution of genetic susceptibility will be evaluated by comparing concordance rates in monozygotic and dizygotic twins. A detailed telephone-administered interview will be used to collect information on exposures and family history, and the role of these factors will be examined using case-control methods in discordant pairs. Shared and nonshared genetic influences on susceptibility to Parkinson's disease, dementia and essential tremor will be investigated by examining co-occurrence of these disorders within first degree relatives. Evaluation of similar hypotheses with respect to Alzheimer's disease is successfully underway in this cohort, under the supervision of one of the co-investigators on this project. A particular strength of this proposal is the shared methods between these two studies.